Polypeptide synthesis may be either solid-phase synthesis (SPPS) or solution-phase synthesis (SP). Progress in solid phase peptide synthesis (SPPS) has always been stimulated by the introduction of new chemistries and new solid supports. Unlike ribosome protein synthesis, protein synthesis by SPPS generally proceeds from the C-terminus to N-terminus. There are several groups of peptides and peptidomimetic compounds characterized by derivatization at the C-terminus of the peptide chain. These groups include several commercially and therapeutically important peptide-acids.
There are several solid supports commercially available for the synthesis of peptide-acids. Presently, two main chemistries used for their synthesis are Boc/Benzyl and Fmoc/t.Butyl chemistry. Recently, Fmoc-chemistry has become preferred over Boc-chemistry because of its greater environmental safety due to avoidance of hazardous and highly toxic hydrofluoric acid, and the use of mild conditions. The most common solid supports for the synthesis of peptide-acids employing Fmoc/t.Butyl chemistry are 4-hydroxymethylphenyloxymethyl polystyrene resin developed by Wang (S. S. Wang, JACS, 95, 1328-1333, 1973; JOC, 40, 1235-1239, 1975), 4-hydroxymethylphenoxyacetyl-poly(dimethylactylamide) resin developed by Atherton (E. Atherton, et al, JCS, Chem. Comm., 1978, 537-539), and 2-chlorotritylchloride (CTC) resin developed by K. Barlos (K. Barlos, et al, IJPPR, 37, 513-520, 1991; 38, 555, 1991).
Each of the commonly utilized resins for the production of peptide acids, however, suffers from drawbacks. First, the preparation of these resins is cumbersome and expensive. Next, the resins often fail to produce the desired peptide in sufficient yield and purity. Finally, acid peptides synthesized using these resins are prone to racemization. A need therefore exists for a solid support that is economical to produce, and that can be used for Fmoc-SPPS synthesis of peptide acids in both high purity and yield with only negligible racemization.